Journal article
Oral losartan treatment improves microvascular endothelial function via nitric oxide-dependent mechanisms in women with a history of preeclampsia
American journal of hypertension, Vol.38(7), pp.459-466
06/16/2025
DOI: 10.1093/ajh/hpaf033
PMCID: PMC12188436
PMID: 40077915
Appears in UI Libraries Support Open Access
Abstract
Women with a history of preeclampsia are at increased risk of developing cardiovascular disease compared with women who had a healthy pregnancy. One potential mechanism underlying this increased risk is microvascular endothelial dysfunction, characterized by reduced nitric oxide (NO)-dependent dilation and is mediated, in part, by increased vasoconstrictor sensitivity to angiotensin II, which persists postpartum. We hypothesized that systemic angiotensin II type 1 receptor (AT1R) inhibition via once-daily oral losartan treatment would 1) improve endothelium- and NO-dependent dilation, and 2) reduce angiotensin II-mediated vasoconstriction, in the microvasculature of women with a history of preeclampsia.
Eleven normotensive women, >12 weeks and ≤5 years postpartum, with a history of preeclampsia participated in a double-blind, placebo-controlled, crossover study. Following 6 weeks of placebo and losartan treatment (50 mg/day), we measured cutaneous vascular conductance responses to graded infusions of acetylcholine (ACh, 10-10-10-1M) alone or with 15mM NG nitro L-arginine methyl ester (L-NAME; NO-synthase inhibitor) to assess endothelium- and NO-dependent dilation, respectively. We also assessed microvascular vasoconstrictor responses to graded infusions of angiotensin II (10-20-10-4M) and norepinephrine (10-12-10-2M).
Losartan treatment increased endothelium- (P<0.001) and NO-dependent (P<0.016) vasodilation compared with placebo. Losartan treatment also reduced angiotensin II-mediated vasoconstriction (P<0.001) compared with placebo, but had no effect on norepinephrine-mediated vasoconstriction (P=0.46).
These data suggest that systemic AT1R-inhibition with oral losartan is a viable, mechanism-specific approach to improve endothelial function and reduce vasoconstrictor sensitivity to angiotensin II in the microvasculature of healthy, normotensive women with a history of preeclampsia.
Details
- Title: Subtitle
- Oral losartan treatment improves microvascular endothelial function via nitric oxide-dependent mechanisms in women with a history of preeclampsia
- Creators
- K S Schwartz - University of IowaD I Jalal - Iowa City VA Health Care SystemA E Stanhewicz - University of Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of hypertension, Vol.38(7), pp.459-466
- DOI
- 10.1093/ajh/hpaf033
- PMID
- 40077915
- PMCID
- PMC12188436
- NLM abbreviation
- Am J Hypertens
- ISSN
- 0895-7061
- eISSN
- 1941-7225
- Publisher
- Oxford University Press; OXFORD
- Grant note
- National Institutes of Health: K99/R00 HL138133, T32 HL007344, UM1TR004403 The University of Iowa Graduate College
This project was supported by the National Institutes of Health Grants K99/R00 HL138133 (to A.E.S.), T32 HL007344 (to K.S.S.), UM1TR004403 (The University of Iowa Clinical and Translational Science Award) and The University of Iowa Graduate College (fellowship to K.S.S.).
- Language
- English
- Electronic publication date
- 03/13/2025
- Date published
- 06/16/2025
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Nephrology; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984799685902771
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